Prostate cancer is the most commonly diagnosed cancer in men, with approximately 1.7 million men in the U.S. having been diagnosed with this condition. Over 200,000 new cases of prostate cancer will be added per year and around 30,000 will die annually, making it the second leading cause of cancer-related deaths in men. The five-year survival rate with prostate cancer is 89%, with this percentage jumping to 100% for patients with localized tumors treated with conventional therapeutic approaches. However, once metastases or hormone-refractory disease develops, therapeutic options are limited. Hence, there is a need to develop new pharmaceuticals for the treatment of metastatic prostate cancer, as well as a need to identify new diagnostic markers that can better discriminate between indolent and aggressive variants of prostate cancer.
Antibody-based therapy using unconjugated, toxin-conjugated or radiolabeled reagents against tumor-associated target antigens has proven beneficial for solid and hematolymphoid neoplasms (Adams 2005; Wu 2005). There are currently 17 monoclonal antibodies (mAbs) approved by the FDA in the US. Of these, eight (five unconjugated and three conjugated) are approved for treatment of cancer (Adams 2005). One key issue with regard to the therapeutic use of monoclonal antibodies has been the response of the human immune system to xenogeneic antibodies. Clinical studies with murine monoclonal antibodies have shown effective tumor targeting, but have also resulted in rapid clearance of the murine antibody due to the generation of a human anti-murine antibody (HAMA) immune response (Schroff 1985; Shawler 1985). The present invention provides humanized antibodies for use in the diagnosis and treatment of prostate cancer with minimal HAMA response.